Studies on the effect of oestrogen treatment on the lipid metabolism of the male chick (gallus domesticus)

The aim of this study was to investigate the early (<48 h) changes in lipid metabolism occuring in the liver after 17B-oestradiol treatment (0.75 mg/100 g body wt.) of the male chick in vivo. An increase in liver weight was observed from 13 - 61 h after oestrogen treatment while an oestrogen-induced increase in the total hepatic DMA content was observed from 37 - 61 h suggesting that the early ( <37 h) liver growth response involved cell hypertrophy where as cell hyperplasia was involved in the later ( <37 h) phase of the response. Oestrogen-induced increases in total liver triacylglycerol and phospholipid were observed from 7 h post-injection while an oestrogen-induced increase in total liver free fatty acid was not observed until after 26 hours. Similarly, total triacylglycerol and phospholipid concentrations in the plasma increased progressively from 7 - 44 h after hormone treatment. Plasma levels of VLDL-triacylglycerol and VLDL-phospho- lipid in similarly-treated birds increased from 13 h and 6 h post- injection, respectively, involving an oestrogen-induced increase in the number of VLDL particles specifically enriched with phospholipid. An oestrogen-induced increase in total free fatty acids in the plasma was not observed at any time post-injection. Analysis of the fatty acid compositions of liver triacylglycerol, VLDL-triacylglycerol and VLDL-phopsholipid, accumulating in oestrogen- treated chicks, revealed that the major oestrogen-induced change was an increase in the level of oleic acid, from 13 hours post-injection. An oestrogen-induced increase in the hepatic activity of the key lipogenic enzyme acetyl-CoA carboxylase (E.C.5.4.1.2) was observed from 24 - 48 h post-injection, involving increased specific activity both with respect to protein and DNA, and total organ activity. The results from the study were correlated in an attempt to determine the early sequence (< 48 h) of oestrogen-induced changes in lipid metabolism

Following the leader: the social character of learning in the Australian Army

The complex environments in which modern soldiers operate require high functioning individuals who are able to adapt and apply their knowledge, skills and experience in a variety of contexts. In order to adapt to challenges associated with increasing complexity and take advantage of its various knowledge bases, the Australian Army has pursued a goal of becoming a learning organisation. Drawing on data collected from 20 unstructured group discussions conducted with over 150 Army personnel, this qualitative study explores the significance of leaders (usually commanding officers but also instructors) as ‘creators’ or ‘shapers’ of learning environments within their units, and the extent to which they facilitate learning by their staff. Findings suggest that the creation of learning environments (within units) often occurs in an ad hoc manner, reflecting the personalities or dispositions of leaders, rather than reflecting an organisational commitment to ‘empowered’ learners. Consequently, soldiers’ abilities to make and learn from mistakes, ask questions, and display initiative fluctuated according to their posting. However, in contrast to the top-down approach to facilitated learning and empowerment often reported in the literature, findings also suggest that subordinates facilitate learning for leaders. Thus, the paper extends the theory of facilitated learning through leadership by acknowledging the recursive nature of empowerment and the agency of subordinates in shaping their learning environment

Identifizierung von potentiellen bakteriologischen Kampfstoffen mit Ramanspektrometrie unter Nutzung von multivariater Statistik

[no abstract

Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to altered dysbindin-1 gene expression

DTNBP1 (dystrobrevin binding protein 1) remains one of the top candidate genes in schizophrenia. Reduced expression of this gene and the protein it encodes, dysbindin-1, has been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia cases. It has not been established, however, if all dysbindin-1 isoforms are reduced in the DLPFC or if the reduction is associated with reduced DTNBP1 gene expression. Using Western blotting of whole-tissue lysates of the DLPFC with antibodies differentially sensitive to the three major isoforms of this protein (dysbindin-1A, -1B, and -1C), we found no significant differences between our schizophrenia cases and matched controls in dysbindin-1A or -1B, but did find a mean 46% reduction in dysbindin-1C in 71% of 28 case-control pairs (p = 0.022). This occurred in the absence of the one DTNBP1 risk haplotype for schizophrenia reported in the US and without alteration in levels of dysbindin-1C transcripts. Conversely, the absence of changes in the dysbindin-1A and -1B isoforms was accompanied by increased levels of their transcripts. We thus found no correspondence between alterations in dysbindin-1 gene and protein expression, the latter of which might be due to posttranslational modifications such as ubiquitination. Reduced DLPFC dysbindin-1C in schizophrenia probably occurs in PSDs, where we find dysbindin-1C to be heavily concentrated in the human brain. Given known postsynaptic effects of dysbindin-1 reductions in the rodent homolog of the prefrontal cortex, these findings suggest that reduced dysbindin-1C in the DLPFC may contribute to cognitive deficits of schizophrenia by promoting NMDA receptor hypofunction

Data collection, analysis methods and equipment for naturalistic studies and requirements for the different application areas. PROLOGUE Deliverable D2.1

Naturalistic driving observation is a relatively new method for studying road safety issues, a method by which one can objectively observe various driver- and accident related behaviour. Typically, participants get their own vehicles equipped with some sort of data logging device that can record various driving behaviours such as speed, braking, lane keeping/variations, acceleration, deceleration etc., as well as one or more video cameras. In this way normal drivers are observed in their normal driving context while driving their own vehicles. Optimally, this allows for observation of the driver, vehicle, road and traffic environments and interaction between these factors. The main objective of PROLOGUE is to demonstrate the usefulness, value, and feasibility of conducting naturalistic driving observation studies in a European context in order to investigate traffic safety of road users, as well as other traffic related issues such as eco-driving and traffic flow/traffic management. The current deliverable aims to develop an inventory of the current and appropriate data collection and data analysis equipment for naturalistic observation studies together with a theoretical analysis of the requirements for different application areas. The deliverable also discusses data quality issues and top level data base management requirements. Among the reviewed literature, maximal use is made of the extensive knowledge and experience that comes from the EU projects FESTA and EuroFOT, the 100car study and the SHRP2 preparatory safety

Mechanisms Underlying the Response to Inequitable Outcomes in Chimpanzees, Pan Troglodytes

Several species of non-human primates respond negatively to inequitable outcomes, a trait shared with humans. Despite previous research, questions regarding the response to inequity remain. In this study, we replicated the methodology from previous studies to address four questions related to inequity. First, we explored the impact of basic social factors. Second, we addressed whether negative responses to inequity require a task, or exist when rewards are given for ‘free’. Third, we addressed whether differences in the experimental procedure or the level of effort required to obtain a reward affected responses. Finally, we explored the interaction between ‘individual’ expectations (based on one’s own previous experience) and ‘social’ expectations (based on the partner’s experience). These questions were investigated in 16 socially-housed adult chimpanzees using eight conditions that varied across the dimensions of reward, effort, and procedure. Subjects did respond to inequity, but only in the context of a task. Differences in procedure and level of effort required did not cause individuals to change their behavior. Males were more sensitive to social than to individual expectation, while females were more sensitive to individual expectation. Finally, subjects also increased refusals when receiving a better reward than their partner, which has not been seen previously. These results indicate that chimpanzees are more sensitive to reward inequity than procedures, and that there is interaction between social and individual expectations that depends upon social factors

Cyclist deaths in London: implications from a safe systems perspective

Cyclist deaths in London: implications from a safe systems perspectiv

Rapid proteasomal elimination of 3-hydroxy-3-methylglutaryl-CoA reductase by interferon-γ in primary macrophages requires endogenous 25-hydroxycholesterol synthesis (in press)

AbstractInterferons (IFNs) play a central role in immunity and emerging evidence suggests that IFN-signalling coordinately regulates sterol biosynthesis in macrophages, via Sterol Regulatory Element-Binding Protein (SREBP) dependent and independent pathways. However, the precise mechanisms and kinetic steps by which IFN controls sterol biosynthesis are as yet not fully understood. Here, we elucidate the molecular circuitry governing how IFN controls the first regulated step in the mevalonate-sterol pathway, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), through the synthesis of 25-Hydroxycholesterol (25-HC) from cholesterol by the IFN-inducible Cholesterol-25-Hydroxylase (CH25H). We show for the first 30-min of IFN stimulation of macrophages the rate of de novo synthesis of the Ch25h transcript is markedly increased but by 120-min becomes transcriptionally curtailed, coincident with induction of the Activating Transcription Factor 3 (ATF3) repressor. We demonstrate ATF3 induction by Toll-like receptors is strictly dependent on IFN-signalling. While the SREBP-pathway dependent rates of de novo transcription of Hmgcr are relatively unchanged in the first 90-min of IFN treatment, we find HMGCR enzyme levels undergo a rapid proteasomal-mediated degradation, defining a previously unappreciated SREBP-independent mechanism for IFN-action. These events precede a sustained marked reduction in Hmgcr RNA levels involving SREBP-dependent mechanisms. We demonstrate that HMGCR proteasomal-degradation by IFN strictly requires the synthesis of endogenous 25-HC and functionally couples HMGCR to CH25H to coordinately suppress sterol biosynthesis. In conclusion, we quantitatively delineate proteomic and transcriptional levels of IFN-mediated control of HMGCR, the primary enzymatic step of the mevalonate-sterol biosynthesis pathway, providing a foundational framework for mathematically modelling the therapeutic outcome of immune-metabolic pathways